The objective of the proposed research is to study pharmacological and behavioral determinants of drug dependence by systematically investigating the control of behavior by scheduled injections of drugs under diverse conditions. The emphasis of this proposal is to analyze how such behavior is influenced by historical factors, especially previous experience with drugs, by suppression of behavior as a result of noxious consequences, and by associated stimulus conditions in the environment. Studies of historical determinants of drug self-administration will evaluate how chronic administration of opiates and barbiturates alters the subsequent control of behavior by these and other classes of drugs (e.g., psychomotor stimulants). Performances developed and maintained under different schedules of drug injection will be compared directly with performances maintained under formally identical conditions by other consequences of behavior, such as presentation of food or electric shock. Studies of the suppression (punishment) of behavior will investigate conditions under which drug self-administration can be attenuated by scheduling noxious stimuli as additional consequences of responding. The suppressant effects of drugs, such as histamine and chlorpromazine, and of other noxious consequences, such as electric shock, on behavior maintained by scheduled injections of drugs and other events will be determined. The effects on suppressed behavior of pretreatment with selected drugs also will be evaluated. Studies of the conrol of behavior by invironmental stimuli associated with self-administered drugs will assess the contribution of such stimuli to the maintenance of persistent drug taking. Optimal and limiting conditions for controlling sequences of behavior by associated stimuli will be investigated under second-order schedules of drug injection. Overall, the proposed research will provide basic information on behavioral and pharmacological factors involved in both the maintenance and suppression of behavior by consequent injection of drugs.